Regulation of Cell Polarity and RNA Localization in Vertebrate Oocytes - International Review of Cell and Molecular Biology - page 147

Polypyrimidine tract binding protein 1 (Ptbp1/VgRBP60/hnRNPI) is
an RRM-containing protein with general roles in RNA metabolism
( Valc´rcel and Gebauer, 1997 ) and binds to the UUUCU motifs in the
gdf1 LE ( Cote et al., 1999; Lewis et al., 2004 ). Both Igf2bp3 and Ptbp1
can associate with gdf1 in the GV and colocalize with gdf1 throughout cyto-
plasmic localization, suggesting that localized RNA-competent RNP
assembly is initiated prior to nuclear export. Interestingly, UV cross-linking
and immunoprecipitation studies have shown that in the GV Ptbp1 binds
directly to gdf1 RNA, whereas Igf2bp3 associates indirectly, but in a manner
that requires Ptbp1 ( Lewis et al., 2008 ). Igf2bp3 later acquires direct binding
in the cytoplasm, suggesting that the arrangement or stoichiometry of
RNA-binding proteins associated with the gdf1 LE is remodeled in the cyto-
plasm ( Lewis et al., 2008 ).
Similarly, Hnrnpab (40LoVE) associates with the gdf1 LE in the GV, and
inhibitory antibody experiments suggest that it is essential for gdf1 localiza-
tion ( Czaplinski et al., 2005 ). Hnrnpab also exhibits protein-protein inter-
actions with Igf2bp3 and Ptbp1, with the latter likely acting as the sequence
specificity determinant ( Czaplinski et al., 2005 ). This protein also interacts
with Khsrp, suggesting that Hnrnpab occupies a central position in RNP
complex assembly ( Kroll et al., 2009 ). Curiously, however, Hnrnpab also
binds to RNAs that are enriched in the animal hemisphere (e.g., an1 ),
suggesting a general role for this protein in regulating the distribution and
activity of cytoplasmic RNAs ( Kroll et al., 2009 ). Phosphorylation of Ptbp1
once it is in the cytoplasm has been proposed to regulate RNP remodeling
( Lewis et al., 2008 ).
Several additional factors are recruited to the gdf1 LE in the cytoplasm,
including the RRM and proline-rich protein Deleted in Azoospermia-
associated protein 1 (Dazap1/Prrp; Zhao et al., 2001 ) and Staufen homolog
1 (Stau1; Kress et al., 2004 ). Staufen is a double-stranded RNA-binding pro-
tein critical for overall RNA localization in Drosophila ( Johnston and
N¨ sslein-Volhard, 1992 ). Stau1 interacts with both gdf1 and Kif5b and over-
expression of a dominant-negative Stau1 disrupts gdf1 localization ( Yoon
and Mowry, 2004 ), suggesting that Stau1 might couple localizing RNPs
to transport machinery. The role of Dazap1 is unclear and loss-of-function
experiments have not been described, although a role for Dazap1 in activat-
ing translation has been proposed ( Smith et al., 2011 ). Similar to Hnrnpab,
Dazap1 associates with some animally enriched mRNAs ( Zhao et al., 2001 ).
One of the main proposed functions of RNA localization is to control
protein synthesis spatially in the cell. Therefore, RNA localization and